Increased Functional Connectivity Between Medulla and Inferior Parietal Cortex in Medication-Free Major Depressive Disorder

Emerging evidence has documented the abnormalities of primary brain functions in major depressive disorder (MDD). The brainstem has shown to play an important role in regulating basic functions of the human brain, but little is known about its role in MDD, especially the roles of its subregions. To uncover this, the present study adopted resting-state functional magnetic resonance imaging with fine-grained brainstem atlas in 23 medication-free MDD patients and 34 matched healthy controls (HC). The analysis revealed significantly increased functional connectivity of the medulla, one of the brainstem subregions, with the inferior parietal cortex (IPC) in MDD patients. A positive correlation was further identified between the increased medulla-IPC functional connectivity and Hamilton anxiety scores. Functional characterization of the medulla and IPC using a meta-analysis revealed that both regions primarily participated in action execution and inhibition. Our findings suggest that increased medulla-IPC functional connectivity may be related to over-activity or abnormal control of negative emotions in MDD, which provides a new insight for the neurobiology of MDD

Abnormal Global Functional Connectivity Patterns in Medication-Free Major Depressive Disorder

Mounting studies have applied resting-state functional magnetic resonance imaging (rs-fMRI) to study major depressive disorder (MDD) and have identified abnormal functional activities. However, how the global functional connectivity patterns change in MDD is still unknown. Using rs-fMRI, we investigated the alterations of global resting-state functional connectivity (RSFC) patterns in MDD using weighted global brain connectivity (wGBC) method. First, a whole brain voxel-wise wGBC map was calculated for 23 MDD patients and 34 healthy controls. Two-sample t-tests were applied to compare the wGBC and RSFC maps and the significant level was set at p < 0.05, cluster-level correction with voxel-level p < 0.001. MDD patients showed significantly decreased wGBC in left temporal pole (TP) and increased wGBC in right parahippocampus (PHC). Subsequent RSFC analyses showed decreased functional interaction between TP and right posterior superior temporal cortex and increased functional interaction between PHC and right inferior frontal gyrus in MDD patients. These results revealed the abnormal global FC patterns and its corresponding disrupted functional connectivity in MDD. Our findings present new evidence for the functional interruption in MDD

The neural basis for understanding imitation-induced musical meaning: the role of the human mirror system

Music can convey meanings by imitating phenomena of the extramusical world, and these imitation-induced musical meanings can be understood by listeners. Although the human mirror system (HMS) is implicated in imitation, little is known about the HMS’s role in making sense of meaning that derives from musical imitation. To answer this question, we used fMRI to examine listeners’ brain activities during the processing of imitation-induced musical meaning with a cross-modal semantic priming paradigm. Eleven normal individuals and 11 individuals with congenital amusia, a neurodevelopmental disorder of musical processing, participated in the experiment. Target pictures with either an upward or downward movement were primed by semantically congruent or incongruent melodic sequences characterized by the direction of pitch change (upward or downward). When contrasting the incongruent with the congruent condition between the two groups, we found greater activations in the left supramarginal gyrus/inferior parietal lobule and inferior frontal gyrus in normals but not in amusics. The implications of these findings in terms of the role of the HMS in understanding imitation-induced musical meaning are discussed

Tractography-based parcellation of the human left inferior parietal lobule

The inferior parietal lobule (IPL) is a functionally and anatomically heterogeneous region. Much of the information about the anatomical connectivity and parcellation of this region was obtained from histological studies on non-human primates. However, whether these findings from non-human primates can be applied to the human inferior parietal lobule, especially the left inferior parietal lobule, which shows evidence of considerable evolution from primates to humans, remains unclear. In this study, diffusion MRI was employed to investigate the anatomical connectivities of the human left inferior parietal lobule. Using a new algorithm, spectral clustering with edge-weighted centroidal voronoi tessellations, to search for regional variations in the probabilistic connectivity profiles of all left inferior parietal lobule voxels with all the rest of the brain identified six subregions with distinctive connectivity properties in the left inferior parietal lobule. Consistent with cytoarchitectonic findings, four subregions were found in the left supramarginal gyrus and two subregions in the left angular gyrus. The specific connectivity patterns of each subregion of the left inferior parietal lobule were supported by both the anatomical and functional connectivity properties for each subregion, as calculated by a meta-analysis-based target method and by voxel-based whole brain anatomical and functional connectivity analyses. The proposed parcellation scheme for the human left inferior parietal lobule and the maximum probability map for each subregion may facilitate more detailed future studies of this brain area

Flexibly adapting to emotional cues: Examining the functional and structural correlates of emotional reactivity and emotion control in healthy and depressed individuals

The ability of emotionally significant stimuli to bias our behaviour is an evolutionarily adaptive phenomenon. However, sometimes emotions become excessive, inappropriate, and even pathological, like in major depressive disorder (MDD). Emotional flexibility includes both the neural processes involved in reacting to, or representing, emotional significance, and those involved in controlling emotional reactivity. MDD represents a potentially distinct form of emotion (in)flexibility, and therefore offers a unique perspective for understanding both the integration of conflicting emotional cues and the neural regions involved in actively controlling emotional systems. The present investigation of emotional flexibility began by considering the functional neural correlates of competing socio-emotional cues and effortful emotion regulation in MDD using both negative and positive emotions. Study 1 revealed greater amygdala activity in MDD relative to control participants when negative cues were centrally presented and task-relevant. No significant between-group differences were observed in the amygdala for peripheral task-irrelevant negative distracters. However, controls demonstrated greater recruitment of the ventrolateral (vlPFC) and dorsomedial prefrontal cortices (dmPFC) implicated in emotion control. Conversely, attenuated amygdala activity for task-relevant and irrelevant positive cues was observed in depressed participants. In Study 2, effortful emotion regulation using strategies adapted from cognitive behaviour therapy (CBT) revealed greater activity in regions of the dorsal and lateral prefrontal cortices in both MDD and control participants when attempting to either down-regulate negative or up-regulate positive emotions. During the down-regulation of negative cues, only controls displayed a significant reduction of amygdala activity. In Study 3, an individual differences approach using multiple regression revealed that while greater amygdala-vmPFC structural connectivity was associated with low trait-anxiety, greater connectivity between amygdala and regions of occipitotemporal and parietal cortices was associated with high trait-anxiety. These findings are discussed with respect to current models of emotional reactivity and emotion control derived from studies of both healthy individuals and those with emotional disorders, particularly depression. The focus is on amygdala variability in differing contexts, the role of the vmPFC in the modulation of amygdala activity via learning processes, and the modulation of emotion by attention or cognitive control mechanisms initiated by regions of frontoparietal cortices

Visual-somatosensory interactions in mental representations of the body and the face

The body is represented in the brain at levels that incorporate multisensory information. This thesis focused on interactions between vision and cutaneous sensations (i.e., touch and pain). Experiment 1 revealed that there are partially dissociable pathways for visual enhancement of touch (VET) depending upon whether one sees one’s own body or the body of another person. This indicates that VET, a seeming low-level effect on spatial tactile acuity, is actually sensitive to body identity. Experiments 2-4 explored the effect of viewing one’s own body on pain perception. They demonstrated that viewing the body biases pain intensity judgments irrespective of actual stimulus intensity, and, more importantly, reduces the discriminative capacities of the nociceptive pathway encoding noxious stimulus intensity. The latter effect only occurs if the pain-inducing event itself is not visible, suggesting that viewing the body alone and viewing a stimulus event on the body have distinct effects on cutaneous sensations. Experiment 5 replicated an enhancement of visual remapping of touch (VRT) when viewing fearful human faces being touched, and further demonstrated that VRT does not occur for observed touch on non-human faces, even fearful ones. This suggests that the facial expressions of non-human animals may not be simulated within the somatosensory system of the human observer in the same way that the facial expressions of other humans are. Finally, Experiment 6 examined the enfacement illusion, in which synchronous visuo-tactile inputs cause another’s face to be assimilated into the mental self-face representation. The strength of enfacement was not affected by the other’s facial expression, supporting an asymmetric relationship between processing of facial identity and facial expressions. Together, these studies indicate that multisensory representations of the body in the brain link low-level perceptual processes with the perception of emotional cues and body/face identity, and interact in complex ways depending upon contextual factors

Functional and structural connectivity of reading networks in the adult brain

Language processing draws upon many distributed regions in the brain. Reading in particular is a skill that emerges from the interaction between brain regions involved in phonological and orthographical processing. This project examined the reading network in adults (18-35 years old) with and without developmental dyslexia. Each participant was assessed on a comprehensive battery of standardised neuropsychological tests, which assessed IQ, reading accuracy and comprehension, spelling, phonological processing, working memory, grammatical understanding, motor coordination, and expressive and receptive language skills. In addition, each participant underwent a non-invasive MRI scan, during which structural and functional images were acquired. More specifically, T1-weighted and diffusion-weighted images were acquired to assess structural networks in the brain, whereas a simple reading task and resting-state fMRI were acquired to assess the functional networks involved in reading. Individuals with dyslexia were found to show reduced activation and reduced connectivity in regions typically associated with skilled reading. Moreover, results suggested that they rely on more effortful processing and attentional mechanisms instead to compensate for their reading difficulties. All in all, results indicated that individuals with developmental dyslexia had abnormal functional and structural brain networks related to reading performance, as well as other functions, such as working memory. These findings suggest that for successful reading remediation, it is important to focus on the integration of phonology with orthography, as well as with working memory. Literacy problems such as developmental dyslexia are thus better characterised as a complex disorder with multiple deficits rather than by a single phonological deficit

Neuroimaging investigations of language to aid paediatric neurosurgical decision making

Childhood onset epilepsy can have a profound effect on cognitive, emotional and behavioural development. As such, early intervention is crucial. Approximately 25-50% of children with epilepsy show resistance to medication however. For these children, neurosurgical intervention may be considered. The decision for surgery is a multi-disciplinary process, including functional Magnetic Resonance Imaging (fMRI) to assess the risk posed by surgery to language. Based on feasibility and behavioural pilot studies, I developed an fMRI task panel optimised for pre-surgical investigations of language in children. This task panel maps different language systems (word retrieval, sentence generation, auditory comprehension and reading comprehension) and localises critical language functions (semantic and syntactic processing). I validated this task panel in healthy children (N=43, 5-16 years). This included assessments of scan quality, comparison of methods for artefact repair, and definition of typical activation patterns. I also piloted the new task panel in a representative sample of children with epilepsy, who were being considered for surgery (N=13, aged 5-16 years). Patient case studies are reported to highlight methodological challenges associated with localisation of critical language regions on an individual basis. Finally, I present experimental analyses which highlight the importance of the ventral system to semantic processing. Activation in this network was reduced in children with epilepsy and predicted language outcome. Further investigation showed prolonged development of specific nodes within this system, supporting multimodal semantic processing (independent of effort and performance accuracy). These regions included ventral occipito-temporal cortex, whose role in semantic processing has so far been underappreciated in the developmental literature. These analyses provide evidence for a core language system, which may be crucial for post-surgical language outcome. The findings from this thesis contribute towards extending and improving the role of fMRI in the surgical decision-making process, with the potential for improving long term outcome. They also contribute to models of typical and atypical language development